Abstracts：
SEZ6 and B7H3 have emerged as promising therapeutic targets for ADCs in small cell lung cancer (SCLC). We developed a bsADC targeting SEZ6 and B7H3, derived from RenLite. The bispecific antibody (bsAb) exhibited high affinity for both human and monkey antigens and effectively bound to multiple SCLC cell lines, demonstrating enhanced internalization compared to the parental monoclonal antibodies (mAbs). The bsAb-vcMMAE conjugate showed remarkable anti-tumor activity in an SCLC cell line-derived xenograft (CDX) model, outperforming benchmarks and the ADCs developed from the individual mAbs targeting SEZ6 or B7H3. Furthermore, in a patient-derived xenograft (PDX) model expressing only B7H3, the bsADC demonstrated significant efficacy. These findings suggest that the bsADC may provide extended benefits for patients. Further studies are currently underway to evaluate a TOPO1i payload for enhanced therapeutic outcomes.
